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Molecular biology reports
Apr, 2022;49 (4): 2723-2733.

High glucose mediates apoptosis and osteogenesis of MSCs via downregulation of AKT-Sirt1-TWIST.

Wenxia Ren, Miaomiao Chai, Mingli Jiang, Yan Zhou, Wensong Tan
Author Information
  1. Wenxia Ren: State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
  2. Miaomiao Chai: State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
  3. Mingli Jiang: State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
  4. Yan Zhou: State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China. zhouyan@ecust.edu.cn. ORCID
  5. Wensong Tan: State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
PMID: 35037196 DOI: 10.1007/s11033-021-07082-6

Abstract

BACKGROUND: Mesenchymal stem cells have been widely used in the treatment of diabetes mellitus. However, hyperglycemia associated with DM promotes cell apoptosis and affects osteogenic differentiation of MSCs in varying degrees, leading to osteoporosis in DM patients. Therefore, in this paper, the effect of high glucose on apoptosis and osteogenesis of MSCs was investigated and underlying mechanism was further determined.
METHODS AND RESULTS: Intracellular ROS levels were determined using probe DCFH-DA. MMP was detected using JC-1 staining. Cell apoptosis was detected using Annexin V-FITC/PI and Flow Cytometer. The expression of genes and protein was detected by qRT-PCR and Western blot respectively. The results showed high glucose induced MSC apoptosis but promoted its osteogenesis. Western blot analysis revealed that high glucose downregulated AKT-Sirt1-TWIST pathway. Activation of Sirt1 via SRT1720 increased TWIST expression, alleviated MSC apoptosis and promoted osteogenesis of MSCs. TWIST knockdown studies demonstrated that inhibition of TWIST intensified high glucose-induced apoptosis but promoted osteogenesis differentiation of MSCs. TWIST is likely to be a new regulator for cross talk between Sirt1 and its downstream targets.
CONCLUSION: Our data demonstrates that high glucose induces MSC apoptosis and enhances osteogenesis differentiation via downregulation of AKT-Sirt1-TWIST.

Keywords

Apoptosis High glucose MSCs Osteogenic differentiation Sirt1-TWIST

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Grants

  1. No. 2018YFC1105800/National Key Research and Development Program of China
  2. No. 81671841/National Natural Science Foundation of China
  3. No. 22221818014/Fundamental Research Funds for the Central Universities

MeSH Term

Apoptosis
Cell Differentiation
Down-Regulation
Glucose
Humans
Osteogenesis
Proto-Oncogene Proteins c-akt
Sirtuin 1

Chemicals

Proto-Oncogene Proteins c-akt
SIRT1 protein, human
Sirtuin 1
Glucose
Journal Article

Word Cloud

Created with Highcharts 10.0.0apoptosisMSCsglucoseosteogenesishighdifferentiationTWISTusingdetectedMSCpromotedAKT-Sirt1-TWISTviaDMdeterminedexpressionWesternblotSirt1downregulationHighBACKGROUND:MesenchymalstemcellswidelyusedtreatmentdiabetesmellitusHoweverhyperglycemiaassociatedpromotescellaffectsosteogenicvaryingdegreesleadingosteoporosispatientsThereforepapereffectinvestigatedunderlyingmechanismMETHODSANDRESULTS:IntracellularROSlevelsprobeDCFH-DAMMPJC-1stainingCellAnnexinV-FITC/PIFlowCytometergenesproteinqRT-PCRrespectivelyresultsshowedinducedanalysisrevealeddownregulatedpathwayActivationSRT1720increasedalleviatedknockdownstudiesdemonstratedinhibitionintensifiedglucose-inducedlikelynewregulatorcrosstalkdownstreamtargetsCONCLUSION:datademonstratesinducesenhancesmediatesApoptosisOsteogenicSirt1-TWIST

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